Background: The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled, prostate cancer prevention study funded by the National Cancer Institute and conducted by SWOG (Southwest Oncology Group). A total of 35,533 men were assigned randomly to one of four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, placebo + placebo). At the time of the trial's development, NIH had invested substantial resources in evaluating the potential benefits of these antioxidants. To capitalize on the knowledge gained from following a large cohort of healthy, aging males on the effects of selenium and/or vitamin E, ancillary studies with other disease endpoints were solicited. Methods: Four ancillary studies were added. Each drew from the same population but had independent objectives and an endpoint other than prostate cancer. These studies fell into two categories: those prospectively enrolling and following participants (studies of Alzheimer's disease and respiratory function) and those requiring a retrospective medical record review after a reported event (cataracts/age-related macular degeneration and colorectal screening). An examination of the challenges and opportunities of adding ancillary studies is provided. The impact of the ancillary studies on adherence to SELECT was evaluated using a Cox proportional hazards model. Results: While the addition of ancillary studies appears to have improved participant adherence to the primary trial, this did not come without added complexity. Activation of the ancillary studies happened after the SELECT randomizations had begun resulting in accrual problems to some of the studies. Study site participation in the ancillary trials varied greatly and depended on the interest of the study site principal investigator. Procedures for each were integrated into the primary trial and all monitoring was done by the SELECT Data and Safety Monitoring Committee. The impact of the early closure of the primary trial was different for each of the ancillary trials. Conclusions: The ancillary studies allowed study sites to broaden the research opportunities for their participants. Their implementation was efficient because of the established infrastructure of the primary trial. Implementation of these ancillary trials took substantial planning and coordination but enriched the overall primary trial.

We investigate a method for interpretation of facades from single images. The emphasis is on the separation of knowledge about facade structure and detection of facade elements. The interpretation task is formulated as a Bayesian inference problem of nding maximum a posteriori estimate. A stochastic model that encompasses the structural knowledge about facade elements is presented and an it is used together with an integrated classi er to determine the correct positions of facade elements. We construct a Markov chain Monte Carlo sampler that solves the problem. Various improvements of the model and sampling algorithm are discussed. Finally, we propose a more general approach for structural recognition using context-free grammars that could be used for other computer vision tasks.

<p>The HIV epidemic in the United States continues to be a significant public health problem, with approximately 50,000 new infections occurring each year. National public health priorities have shifted in recent years towards targeted HIV prevention efforts among people living with HIV/AIDS (PLWHA) that include: increasing engagement in and retention in care, improving HIV treatment adherence, and increasing screening for and treatment of substance use and psychological difficulties. This study evaluated the efficacy of Positive Choices (PC), a brief, care-based, theory-driven, 3-session counseling intervention for newly HIV-diagnosed men who have sex with men (MSM), in the context of current national HIV prevention priorities. The study involved secondary analysis of data from a preliminary efficacy trial of the PC intervention (n=102). Descriptive statistics examined baseline substance use, psychological characteristics and strategies, and care engagement and HIV-related biological outcomes. Generalized Estimating Equations (GEE) examined longitudinal changes in these variables by study condition. Results indicated that PC improved adherence to HIV treatment, but increased use of illicit drugs, specifically amyl nitrates and other stimulant drugs; additionally, moderation analyses indicated differences in patterns of change over time in viral load by baseline depression status. Implications of the findings and suggestions for future research are discussed.</p> / Dissertation

Thesis advisor: Judith Shindul-Rothschild / Clinical Characteristics Of People In Randomized Clinical Trials Of First Episode Schizophrenia Spectrum Disorders: Attrition Versus Non-Attrition Groups Submitted by Joanne D. Wojcik PhD, RN Dissertation Advisor Judith Shindul-Rothschild, PhD, RN Abstract Background: Early identification of psychosis and intensive treatment has been the focus of the treatment of people with a first episode (FE) schizophrenia spectrum disorder (SSD). Attrition rates in studies of people in the first episode are high, which makes it difficult to understand the meaning of the study outcomes. High attrition rates affect the validity of a study by decreasing its power and the study's ability to detect differences between treatment groups. Additionally, the people who leave a study may be different from those who stay in demographic, illness and treatment characteristics. Method: This study is a secondary analysis of a group of FE SSD participants enrolled in one of three separate double-blind, randomized, drug trials. The variables were first analyzed across the three drug study data sets to determine if the patient populations are comparable across the three studies to allow for the merging of the data. Exploratory and descriptive statistics of study participants were conducted in a comparison of the three studies, for the merged group, and for the attrition and non-attrition groups. Effect sizes (Cohen's d) were calculated for each variable in the individual studies and in the merged dataset for the magnitude of difference between the attrition and non-attrition groups. Results: The three studies were merged after analysis found no consistent difference in demographic and illness characteristics between the three studies. There was no significant difference between the attrition and non-attrition groups in the merged data in demographic and illness characteristics. Treatment characteristics consistently found lack of efficacy and patient withdrawal of consent to be the two most frequent reasons for attrition from the studies. In addition, participants receiving a typical agent were less likely to complete the study. Effect size calculations found attrition group to more likely be Caucasian, with a lower median income. The attrition group had more years of education, but was not in school in the year previous to hospitalization. Conclusion: Historically, attrition is a major problem in clinical trials of people in a first episode of schizophrenia spectrum disorders. People receiving typical antipsychotic medication are more likely to leave a study. Most common reasons for attrition include lack of efficacy and withdrawal of consent / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

With the wide usage of online tutoring systems, researchers become interested in mining data from logged files of these systems, so as to get better understanding of students. Varieties of aspects of students’ learning have become focus of studies, such as modeling students’ mastery status and affects. On the other hand, Randomized Controlled Trial (RCT), which is an unbiased method for getting insights of education, finds its way in Intelligent Tutoring System. Firstly, people are curious about what kind of settings would work better. Secondly, such a tutoring system, with lots of students and teachers using it, provides an opportunity for building a RCT infrastructure underlying the system. With the increasing interest in Data mining and RCTs, the thesis focuses on these two aspects. In the first part, we focus on analyzing and mining data from ASSISTments, an online tutoring system run by a team in Worcester Polytechnic Institute. Through the data, we try to answer several questions from different aspects of students learning. The first question we try to answer is what matters more to student modeling, skill information or student information. The second question is whether it is necessary to model students’ learning at different opportunity count. The third question is about the benefits of using partial credit, rather than binary credit as measurement of students’ learning in RCTs. The fourth question focuses on the amount that students spent Wheel Spinning in the tutoring system. The fifth questions studies the tradeoff between the mastery threshold and the time spent in the tutoring system. By answering the five questions, we both propose machine learning methodology that can be applied in educational data mining, and present findings from analyzing and mining the data. In the second part, we focused on RCTs within ASSISTments. Firstly, we looked at a pilot study of reassessment and relearning, which suggested a better system setting to improve students’ robust learning. Secondly, we proposed the idea to build an infrastructure of learning within ASSISTments, which provides the opportunities to improve the whole educational environment.

BACKGROUND: Preoperative anxiety commonly occurs in young children prior to anesthesia induction. This anxiety is associated with poor post-operative outcomes such as increases in emergence delirium occurrence and post-operative pain. Studies have demonstrated varying effectiveness of interventions such as clowns and video games used to engage and distract children from their anxiety. Anesthesiologists at Lucile Packard Children’s Hospital have designed a new screen-based modality, called the Bedside Entertainment Theatre (BERT), to distract children from their anxiety. OBJECTIVE: The aim of this study is to examine the anxiety-relieving efficacy of BERT against a hand-held electronic tablet, another screen-based form of entertainment used to alleviate preoperative anxiety in children at the hospital. METHODS: Children aged 4-10 undergoing non-emergent outpatient surgery at Lucile Packard Children’s Hospital and their primary caregiver were recruited for the study. Measures were taken at 5 timepoints from children, parents, and clinicians: in the preoperative holding area (T1), at entrance to the OR (T2), at induction (T3), after emergence from anesthesia (T4), and at a 1-week follow up (T5). Primary outcomes were preoperative anxiety, assessed by the modified Yale Preoperative Anxiety Scale (mYPAS) and Child Fear Scale (CFS), and induction compliance, assessed by the Induction Compliance Checklist (ICC). Secondary outcomes were emergence delirium, measured by the Pediatric Anesthesia Emergence Delirium Scale (PAED) and post-operative pain, measured by the Parents’ Post-operative Pain Measure (PPPM) and a Memory Recall Interview. Child covariates were temperament, measured by the Emotionality Activity Sociability Temperament Survey (EAS-TS) and the Children’s Behavior Questionnaire- Very Short Form (CBQ-VSF), and state-trait anxiety, measured by the Child State-Trait Anxiety Inventory (STAIC). Caregiver covariates were state-trait anxiety, measured by the State-Trait Anxiety Inventory (STAI) and caregiver pain catastrophizing about their child, measured by the Pain Catastrophizing Scale- Parent State (PCS-P State). This study is currently ongoing and plans to recruit 60 participants. Parent, child, and clinician satisfaction with usage of either intervention was also assessed. RESULTS: There were no significant differences between mean preoperative anxiety scores of BERT and tablet users at all pre-induction timepoints. There was a significant increase in mean preoperative anxiety scores in BERT users from T1 to T2 and T1 to T3. There was also a significant increase in mean preoperative anxiety scores from T1 to T3 for tablet users. There were no other significant differences in primary and secondary outcomes between interventions. Only post-surgery PCS-P State scores for BERT users correlated with mYPAS scores at T3 (p < 0.05). No other measured covariates correlated with preoperative anxiety scores (p > 0.05). CONCLUSIONS: Although preliminary results do not show differences between the interventions in relieving preoperative anxiety, there may be potential insights gained in how both interventions affect anxiety at different preoperative timepoints. Statistical analysis with the full sample population will be necessary to draw stronger conclusions. / 2018-07-11T00:00:00Z

<p>The aims of the thesis were to</p><p>• explore whether radical prostatectomy is beneficial compared with watchful waiting in survival and disease progression</p><p>• find possible effect modifiers</p><p>• evaluate a protocol of multiple biopsies and investigate if men with previous benign prostate biopsies are a group at risk for later prostate cancer</p><p>• inquire into patients’ and clinicians’ experiences of randomization in order to find out what made this study possible to conduct, and thereby contribute to improve randomization in the future</p><p>The background material was a large randomized clinical trial, the Scandinavian Prostatic Cancer Group Study Number 4, or SPCG-4, which was open for inclusion from February 1989 through December 1999. It comprised 695 men in Sweden, Finland and Iceland who had localized prostate cancer and were randomized to either radical prostatectomy or watchful waiting. </p><p>After a mean follow-up time of 6.2 years the first analyses, according to intention-to-treat, showed that radical prostatectomy reduced disease specific mortality, risk of metastases and risk of local progression but did not statistically significantly reduce overall mortality. </p><p>The second analyses confirmed our earlier findings and furthermore, at ten years, radical prostatectomy also statistically significantly reduced overall mortality. Age appeared as an independent effect modifier that will be further investigated.</p><p>A total of 547 men, with a suspicion of prostate cancer that had undergone multiple biopsies, and whose biopsies had benign histology were later compared with the background population to evaluate whether they were a group at risk of developing prostate cancer. Within six years of follow-up, there was no increased risk of prostate cancer.</p><p>Patients as well as clinicians used individual strategies to cope with the situation. The randomizing clinician has to understand the patient’s strategy and his expectations in order to individualize the information accordingly.</p>

BACKGROUND: In a 2006 WHO report, diarrheal diseases ranked second among conditions afflicting children. Pediatric acute diarrhea, although most often the result of a gastrointestinal infection, can also occur as a result of antibiotic exposure. This is often referred to as antibiotic-associated diarrhea (AAD). Previous research suggests that probiotics may be effective in the treatment or prevention of various types of PAD. METHODS: The first study involved a systematic review and meta-analysis of RCTs involving probiotics as an adjunct to antibiotics for preventing AAD in children. The second study was a systematic review of definitions and primary outcome measures employed in RCTs of PAD. The third study used a modified Delphi consensus procedure to develop a new instrument for evaluating the severity of PAD. The study involved steering committee discussions (phase 1) and two electronic surveys (phase 2 and 3) of leading experts in measurement and clinical gastroenterology. RESULTS: The per protocol meta-analysis of ten RCTs significantly favored probiotics to prevent the incidence of diarrhea (NNT = 10). However, this effect did not withstand ITT analysis and among included trials there was considerable inconsistency regarding definitions for the reviews primary outcome measure, the incidence of diarrhea. Study two identified 121 RCTs that reported 62 unique definitions of diarrhea, 64 unique definitions of diarrhea resolution and 62 unique primary outcome measures. Thirty-one trials used grading systems to support outcome evaluation. However, none of the trials (or their citations) reported evidence of their validation. In study three experts agreed on the inclusion of five attributes containing 13 items. Attributes proposed for the IPADDS include: Diarrhea Frequency and Duration, Vomiting Frequency and Duration, Fever, Restrictions in Normal Daily Activities and Dehydration. CONCLUSION: It is premature to draw a valid conclusion about the efficacy of probiotics for pediatric AAD. Definitions of diarrhea and primary outcome measures in RCTs of PAD are heterogeneous and lack evidence of validity. The third study represents content validity evidence for IPADDS. A numerical scoring system needs to be added and further empirical evidence of reliability and validity are required. / Experimental Medicine

This study was directed toward improving the balance and consistency of student participation by thinning, randomizing, and delaying credit for student participation. Each of three sections of a large college course (n = 55) employed a different contingency for choosing the days in which participation credit was awarded: (1) credit units identified ahead of time, (2) credit units announced at the end of the course, and (3) credit units randomly selected by students at the end of the course. For all contingencies, random selection of 2 out of 4 discussion days in each credit unit occurred at the conclusion of the course. The study compared the effects of the different credit contingencies on the percentage of students participating at selected levels across days and units. Students recorded their individual comments during class discussion. External raters recorded the number of timely and repetitious comments per student, the number of comprehension and factual questions posed by instructors, and the amount of positive and negative feedback provided to each student. Results showed that when students knew which units would provide participation credit (Section A), the percentage of non-participants and dominant participants decreased, while the percentage of credit-level participants increased. These results are consistent with previous research (e.g., Krohn et al, 2010) reporting balanced participation when students know in advance the specific units when credit is available for participation. Conversely, when students did not know until the end of the semester which units would provide credit (Sections B and C), participation patterns remained relatively similar across units. The percentage of participants at different levels in Sections B and C fell between the percentages for credit and non-credit levels in Section A. A 50-item survey also was given at the beginning of the course to assess student beliefs concerning class participation. The total survey scores significantly predicted student placement into low- or high-participation groups throughout the course. Logistic regression analyses showed that the primary factor, Personal History and Preference regarding Class Participation, better predicted membership in the low-participant group in non-credit units and membership in the high-participant group in credit units in Section A.

The aims of the thesis were to • explore whether radical prostatectomy is beneficial compared with watchful waiting in survival and disease progression • find possible effect modifiers • evaluate a protocol of multiple biopsies and investigate if men with previous benign prostate biopsies are a group at risk for later prostate cancer • inquire into patients’ and clinicians’ experiences of randomization in order to find out what made this study possible to conduct, and thereby contribute to improve randomization in the future The background material was a large randomized clinical trial, the Scandinavian Prostatic Cancer Group Study Number 4, or SPCG-4, which was open for inclusion from February 1989 through December 1999. It comprised 695 men in Sweden, Finland and Iceland who had localized prostate cancer and were randomized to either radical prostatectomy or watchful waiting. After a mean follow-up time of 6.2 years the first analyses, according to intention-to-treat, showed that radical prostatectomy reduced disease specific mortality, risk of metastases and risk of local progression but did not statistically significantly reduce overall mortality. The second analyses confirmed our earlier findings and furthermore, at ten years, radical prostatectomy also statistically significantly reduced overall mortality. Age appeared as an independent effect modifier that will be further investigated. A total of 547 men, with a suspicion of prostate cancer that had undergone multiple biopsies, and whose biopsies had benign histology were later compared with the background population to evaluate whether they were a group at risk of developing prostate cancer. Within six years of follow-up, there was no increased risk of prostate cancer. Patients as well as clinicians used individual strategies to cope with the situation. The randomizing clinician has to understand the patient’s strategy and his expectations in order to individualize the information accordingly.